Content and Format of INDs for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-Derived Products. Questions and Answers: Guidance for Industry Q&A

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Guidance for Industry
Q & A
Content and Format of INDs for Phase 1 Studies
of Drugs, Including
Well-Characterized, Therapeutic,
Biotechnology-Derived Products
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biological Evaluation and Research (CBER)
October 2000
Pharmacology/Toxicology

Guidance for Industry
Q & A
Content and Format of INDs for Phase 1 Studies of
Drugs, Including Well-Characterized, Therapeutic,
Biotechnology-Derived Products
Additional copies are available from:
Office of Training and Communications
Division of Communications Management
Drug Information Branch, HFD-210
5600 Fishers Lane
Rockville, MD 20857
(Tel) 301-827-4573
(Internet) http://www.fda.gov/cder/guidance/index.htm
or
Office of Communication, Training and
Manufacturers Assistance, HFM-40
Center for Biologics Evaluation and Research
Food and Drug Administration
1401 Rockville Pike, Rockville, MD 20852-1448
Internet: http://www.fda.gov/cber/guidelines.htm.
Fax: 1-888-CBERFAX or 301-827-3844
Mail: the Voice Information System at 800-835-4709 or 301-827-1800
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biological Evaluation and Research (CBER)
October 2000
Pharmacology/Toxicology

Guidance for Industry1
Q & A on
Content and Format of INDs for Phase 1 Studies of Drugs,
Including Well-Characterized, Therapeutic,
Biotechnology-Derived Products
I. INTRODUCTION
This guidance is intended to clarify when sponsors should submit final, quality-assured toxicology
reports and/or update the Agency on any changes in findings since submission of non-quality-assured
reports or reports based on non-quality-assured data.
In November 1995, FDA published a guidance for industry entitled Content and Format of
Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-
Characterized, Therapeutic, Biotechnology-Derived Products. The guidance states that
If final, fully quality-assured individual study reports are not available at the time of
IND submission, an integrated summary report of toxicologic findings based on the
unaudited draft toxicologic reports of completed animal studies may be
submitted.… [...] full toxicology department individual study reports should be
available to FDA, upon request, and individual study reports should be available to
FDA, upon request, as final, fully quality-assured documents within 120 days of
the start of the human study… [emphasis added].
If the integrated summary is based upon unaudited draft reports, sponsors should
submit an update to their integrated summary 120 days after the start of the human
study(ies)….2
1 This guidance has been prepared by the Pharmacology and Toxicology staff, Office of Review Management ORM),
Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) in
the Food and Drug Administration.
This guidance represents the Food and Drug Administration=s current thinking on this topic. It does
not create or confer any rights for or on any person and does not operate to bind FDA or the public.
An alternative approach may be used if such approach satisfies the requirements of the applicable
statutes, regulations, or both.

There has been some confusion over when the 120-day clock starts, specifically, whether it means 120
days after the start of the clinical trial, or 120 days after the submission of the toxicology information.
Q: How does FDA measure the start of the 120-day period within which sponsors should
submit updates to their integrated summaries?
A: The Agency measures the 120-day period based on the Agency's receipt (date of receipt
stamped on the IND submission) of the integrated summary report including the toxicology
information. If the sponsor does not submit the final, quality-assured report and update at this
time, the sponsor should make the final, quality-assured report available upon the request of the
Agency and update the Agency on any changes in the findings. In any case, the final, quality-
assured report should be submitted with the NDA.
The Agency believes that 120 days from submission of an integrated toxicology summary should
provide sponsors with adequate time to complete a final, quality-assured document. Because the
Agency assumes that clinical studies will generally be initiated immediately following the initial 30-day
clock (or upon submission of the protocol for an existing IND), the intention of the 120-day allowance
is to encourage the initiation of clinical studies by, in effect, allowing earlier submissions of clinical
protocols based on unaudited reports.
2 See guidance, section III(G)(2), Toxicology: Integrated Summary.